Genetic Analysis of Neisseria meningitidis Sequence Type 7 Serogroup X Originating from Serogroup A

Abstract

Neisseria meningitidis causes meningococcal disease, often resulting in fulminant meningitis, sepsis, and death. Vaccination programs have been developed to prevent infection of this pathogen, but serogroup replacement is a problem. Capsular switching has been an important survival mechanism for N. meningitidis, allowing the organism to evolve in the present vaccine era. However, related mechanisms have not been completely elucidated. Genetic analysis of capsular switching between diverse serogroups would help further our understanding of this pathogen. In this study, we analyzed the genetic characteristics of the sequence type 7 (ST-7) serogroup X strain that was predicted to arise from ST-7 serogroup A at the genomic level. By comparing the genomic structures and sequences, ST-7 serogroup X was closest to ST-7 serogroup A, whereas eight probable recombination regions, including the capsular gene locus, were identified. This indicated that serogroup X originated from serogroup A by recombination leading to capsular switching. The recombination involved approximately 8,540 bp from the end of the ctrC gene to the middle of the galE gene. There were more recombination regions and strain-specific single-nucleotide polymorphisms in serogroup X than in serogroup A genomes. However, no specific gene was found for each serogroup except those in the capsule gene locus.

Meningococcal disease surveillance in the Asia–Pacific region (2020): The global meningococcal initiative

“…65 , 66 Between the donor and recipient strains, eight potential recombination sites were identified, indicating the capsular switch occurred through a recombination involving 8540 base pairs spanning from the ctrC to the galE genes. 65 It has also been shown this switch can occur at high frequency (6.3 × 10 −6 per bacterium per μg of DNA). 66 A MenC cc4821 hyperinvasive strain has increasingly been isolated since 2003 67 and cc4821 has also been identified among MenB isolates.…”

Meningococcal disease and control in China: Findings and updates from the Global Meningococcal Initiative (GMI)

“…[30][31][32] In 2016, a single case of serogroup Y Nm was isolated from a patient in Tianjin; however, there have since been no recorded serogroup Y MD (MenY) cases indigenous to China. 32 Further, capsular switching has been described among meningococcal serogroups A and C, 33 serogroups A and X 34 and serogroups B and C. 27,35 Following the sequencing of whole capsular and surrounding genes and the identification of potential recombination sites, it was determined that ST-7 MenC was likely to have evolved from ST-7 MenA as a result of capsular gene rearrangement. 33 In addition, ST-7 MenX was determined as likely to have originated from ST-7 MenA via recombination leading to capsular switching following the identification of probable recombination regions during genomic analysis, however only one case was recorded.…”

“…33 In addition, ST-7 MenX was determined as likely to have originated from ST-7 MenA via recombination leading to capsular switching following the identification of probable recombination regions during genomic analysis, however only one case was recorded. 34 The continued epidemiological and sentinel surveillance of MD provides an overview of trends and prevalence of different meningococcal serogroups and is important in order to inform vaccination and disease planning.…”

“…While there are many recorded cases of serogroups A, B and C across China, 38 MenX has only been identified in MD patients in two provinces. 30,34 Currently, 12 vaccines are freely available via the Chinese EPI for the control of 15 infectious diseases, including MD and hepatitis A. The MenA polysaccharide vaccine and the MenA plus MenC polysaccharide vaccine are available via the routine immunization program at no extra cost to individuals.…”

Neisseria meningitidisSerogroup X ST-5799 (ST-22 complex) in Turkey: A unique pediatric case

“…Nonetheless, some recombination events are reported between serogroups X and A recently. 18 The serogroup X-associated sublineage identified in the present study is also a product of capsule switching, probably from serogroup W, though confirmation of this would require further analysis. This case also highlightes the importance of continued surveillance because of the import of new or epidemic clones of N. meningitidis, including MenX, which is not included in the available meningococcal vaccines.…”